Site Navigation

Site Mobile Navigation

Gene Factor Tied to Severity of Lupus

ONE of the many puzzling aspects of the autoimmune disease lupus is the wide variation in severity among patients, particularly across racial lines: blacks, who are three times as likely as whites to develop lupus, are also more prone to suffer serious complications, especially kidney disease.

Researchers have found an explanation for part of the racial difference. Blacks are more likely to have inherited a gene that increases their risk of kidney problems if they get lupus, according to a study published in the current issue of The Journal of Clinical Investigation. Directed by Dr. Jane Salmon of Cornell University's Hospital for Special Surgery in New York, the study included nearly 400 blacks at five medical centers, two of them in New York and the others in Houston, Chicago and Bethesda, Md.

Two hundred thousand to two million Americans have lupus. Ninety percent of the patients are women. The cause of the disease is unknown, though researchers suspect that a combination of about five genes may be responsible. In the 1950's lupus was often fatal, but improvements in treatment, often with steroids, have greatly increased patients' life spans.

The disease develops when the immune system, which normally attacks foreign substances like viruses and bacteria, reacts to the patient's own body as if it were foreign. The system produces antibodies directed against the patient's cells, and those antibodies and substances from the cells then combine to form immune complexes, which are circulated through the bloodstream and deposited in various tissues and organs.

The buildup of immune complexes sets off inflammation, which can damage the joints, skin, kidneys, lungs, heart, nervous system and blood vessels. The degree of damage depends on how well the patient's body can rid itself of the immune complexes: people who cannot clear them have the severest illness. They are particularly prone to kidney disease.

Dr. Salmon and her colleagues studied black patients, with and without lupus, to determine whether an inherited difference in the ability to get rid of the complexes was linked to the kidney complication known as lupus nephritis.

An error has occurred. Please try again later.

You are already subscribed to this email.

They looked at a gene that controls the production of a protein known as an Fc receptor, which enables phagocytes, a type of white blood cell, to capture immune complexes and remove them from the body. The gene for the receptor comes in two forms: one codes for receptors that are good at capturing immune complexes, and one produces receptors that do not do the job.

Compared with healthy black subjects, those with lupus were more likely to have inherited the gene for the inefficient receptors. The gene was most common of all among the black lupus patients who also had nephritis. (An earlier study failed to detect such a difference in white Americans.)

The link is not strong enough to justify screening black lupus patients for the gene at this time, Dr. Salmon said. But eventually, doctors may be able to use a genetic difference like this to predict which patients with lupus are at risk for kidney disease, and to monitor them more closely in order to begin treatment early enough to prevent kidney damage.

"As a first step towards understanding specific genes that contribute to lupus, this is a very important study," said Dr. Timothy Behrens, a lupus specialist at the University of Minnesota. "This gene may be an important modifier of the disease course, if not one of the primary genes involved in causing lupus. And we're desperately looking for any genes we know the function of that will help us understand the pathophysiology of this disease."